High efficacy of PD-1 inhibitor after initial failure of PD-L1 inhibitor in Relapsed/Refractory classical Hodgkin Lymphoma.

PURPOSE: We sought to understand the clinical course and molecular phenotype of patients who showed disease progression after programmed cell death ligand 1 (PD-L1) inhibitor treatment but subsequently responded to PD-1 inhibitor treatment. We also explored the response to PD-1-axis targeted therapy of classical Hodgkin lymphoma (cHL) according to genetically driven PD-L1 and programmed cell death ligand 2 (PD-L2) expression. METHODS: Five patients in a phase II clinical trial of CS1001 (PD-L1 inhibitor) for relapsed or refractory (R/R) cHL were retrospectively reviewed. Formalin-fixed, paraffin-embedded whole tissues from the five patients were evaluated for 9p24.1 genetic alterations based on FISH and the expression of PD-L1, PD-L2, PD-1, major histocompatibility complex (MHC) class I-II, and the tumor microenvironment factorsCD163 and FOXP3 in the microenvironmental niche, as revealed by multiplex immunofluorescence. RESULTS: All five patients showed primary refractory disease during first-line treatment. Four patients received PD-1 inhibitor after dropping out of the clinical trial, and all demonstrated at least a partial response. The progression-free survival ranged from 7 to 28 months (median = 18 months), and 9p24.1 amplification was observed in all five patients at the PD-L1/PD-L2 locus. PD-L1 and PD-L2 were colocalized on Hodgkin Reed-Sternberg (HRS) cells in four of the five (80%) patients. There was differential expression of PD-L1 and PD-L2 in cells in the tumor microenvironment in cHL, especially in HRS cells, background cells and tumor-associated macrophages. CONCLUSIONS: PD-L1 monotherapy may not be sufficient to block the PD-1 pathway; PD-L2 was expressed in HRS and background cells in cHL. The immunologic function of the PD-L2 pathway in anti-tumor activity may be underestimated in R/R cHL. Further study is needed to elucidate the anti-tumor mechanism of PD-1 inhibitor and PD-L1 inhibitor treatment.

[Treatment of serious burst thoracolumbar fracture with posterior pedicle screw fixation, transpedicular bone grafting and vertebral canaloplasty].

OBJECTIVE: To study the clinical results of posterior pedicle screw fixation, transpedicular bone grafting and vertebral canaloplasty with ilium autografting in treating serious burst thoracolumbar fracture. METHODS: From March 2004 to March 2008,10 patients with serious burst thoracolumbar fracture, including 7 males and 3 females with age for 24-58 years (mean 41 years)were treated by posterior pedicle screw fixation, transpedicular bone grafting and total laminectomy with preservation of spinal process and vertebral canaloplasty with ilium autografting. The operative effects were assessed according to Frankel classification and radiologic results. RESULTS: All patients were followed up from 1 to 4 years. There was no loosening or broken in instrumentation. The anterior edge height of the fractured vertebrae body was restored from (21.00 +/- 12.00)% to (95.00 +/- 4.20)%, and the posterior edge height of the fractured vertebrae body was restored from (70.00 +/- 15.00)% to (96.00 +/- 3.20)% postoperatively, which both demonstrated improvement compared with preoperative instance (P < 0.01). The Cobb angle was restored from (32.80 +/- 8.20) degrees to (4.20 +/- 1.60) degrees which also demonstrated improvement compared with the preoperative Cobb angle (P < 0.01). At least one grade recovery was observed in all cases except one patient with preoperative Frankel A degree. The result of Denis classification, P1, had 4 cases, P2 had 4, P3 had 1, P4 had 1. CONCLUSION: Posterior pedicle screw fixation, transpedicular bone grafting and vertebral canaloplasty can obtain satisfactory results treating serious burst thoracolumbar fractures. It is a feasible method with advantages of simple operation, good efficacy, preservation of structure of posterior column which should be applied clinically.